title: Inhalation of diesel exhaust does not exacerbate cardiac hypertrophy or heart failure in two mouse models of cardiac hypertrophy.
abstract: BACKGROUND
  Strong associations have been observed between exposure to fine ambient particulate matter (PM2.5) and adverse cardiovascular outcomes. In particular, exposure to traffic related PM2.5 has been associated with increases in left ventricular hypertrophy, a strong risk factor for cardiovascular mortality. As much of traffic related PM2.5 is derived from diesel exhaust (DE), we investigated the effects of chronic DE exposure on cardiac hypertrophy and heart failure in the adult mouse by exposing mice to DE combined with either of two mouse models of cardiac hypertrophy: angiotensin II infusion or pressure overload induced by transverse aortic banding.
  
  
  METHODS
  Wild type male C57BL/6 J mice were either infused with angiotensin II (800 ng/kg/min) via osmotic minipump implanted subcutaneously for 1 month, or underwent transverse aortic banding (27 gauge needle 1 week for observing acute reactions, 26 gauge needle 3 months or 6 months for observing chronic reactions). Vehicle (saline) infusion or sham surgery was used as a control. Shortly after surgery, mice were transferred to our exposure facility and randomly assigned to either diesel exhaust (300 or 400 μg/m(3)) or filtered air exposures. After reaching the end of designated time points, echocardiography was performed to measure heart structure and function. Gravimetric analysis was used to measure the ventricular weight to body weight ratio. We also measured heart rate by telemetry using implanted ambulatory ECG monitors.
  
  
  RESULTS
  Both angiotensin II and transverse aortic banding promoted cardiac hypertrophy compared to vehicle or sham controls. Transverse aortic banding for six months also promoted heart failure in addition to cardiac hypertrophy. In all cases, DE failed to exacerbate the development of hypertrophy or heart failure when compared to filtered air controls. Prolonged DE exposure also led to a decrease in average heart rate.
  
  
  CONCLUSIONS
  Up to 6-months of DE exposure had no effect on cardiac hypertrophy and heart function induced by angiotensin II stimulation or pressure overload in adult C57BL/6 J mice. This study highlights the potential importance of particle constituents of ambient PM2.5 to elicit cardiotoxic effects. Further investigations on particle constituents and cardiotoxicity are warranted.
authors.affiliation: Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA, USA. mtchin@u.washington.edu.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Liu
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Chien
authors.forename: Ivan O
authors.initials: IO
authors.lastname: Medvedev
authors.forename: Chad S
authors.initials: CS
authors.lastname: Weldy
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Luchtel
authors.forename: Michael E
authors.initials: ME
authors.lastname: Rosenfeld
authors.forename: Michael T
authors.initials: MT
authors.lastname: Chin
mesh_terms: D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000000981:diagnostic imaging; D004195:Disease Models, Animal; D018450:Disease Progression; D004452:Echocardiography; D006333:Heart Failure / Q000139:chemically induced* / Q000000981:diagnostic imaging; D006339:Heart Rate / Q000187:drug effects; D019570:Inhalation Exposure / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D013997:Time Factors; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D001335:Vehicle Emissions; D000804:Angiotensin II